What is the recommended dose of hydroxyzine (antihistamine) for a relatively healthy adult with no significant medical history for sleep?

Hydroxyzine Dosing for Sleep in Adults

For a relatively healthy adult using hydroxyzine specifically for sleep, the recommended dose is 50 mg taken at bedtime. 1

FDA-Approved Dosing for Sedation

The FDA label explicitly states that hydroxyzine is indicated "as a sedative when used as a premedication and following general anesthesia" at a dose of 50 to 100 mg for adults. 1 While this indication refers to perioperative sedation rather than chronic insomnia, it establishes the sedative dosing range.

Evidence Supporting Bedtime Dosing Strategy

Bedtime dosing of hydroxyzine 50 mg once nightly is superior to divided dosing throughout the day because it maintains antihistamine efficacy while mitigating daytime psychomotor impairment. 2 A controlled study demonstrated that hydroxyzine 50 mg at bedtime did not cause statistically significant degradation in reaction time tests the following day, unlike divided dosing regimens. 2

• Hydroxyzine 50 mg at bedtime maintained histamine H1-receptor antagonism the following morning without prolonging reaction times. 2
• Although subjective symptoms like drowsiness and dry mouth remained significant compared to placebo (P = .0001 and .001 respectively), these were less pronounced than with divided dosing of 25 mg twice daily. 2

Critical Safety Considerations

Hydroxyzine is NOT recommended as first-line treatment for chronic insomnia. The American Academy of Sleep Medicine explicitly states that over-the-counter antihistamines (including prescription antihistamines like hydroxyzine) are not recommended for insomnia due to lack of efficacy data and safety concerns. 3

Why Hydroxyzine Should Be Avoided for Chronic Insomnia:

• Performance impairment persists despite bedtime dosing. First-generation antihistamines like hydroxyzine cause daytime drowsiness, decreased alertness, and performance impairment even when dosed only at bedtime, because their metabolites have prolonged plasma half-lives. 4
• Driving impairment is significant. A large epidemiologic study found drivers responsible for fatal automobile accidents were 1.5 times more likely to be taking first-generation antihistamines. 4 Hydroxyzine specifically worsens driving performance, which is further exacerbated by cellular phone use. 4
• Anticholinergic effects are problematic. Hydroxyzine causes dry mouth, dry eyes, constipation, urinary retention, and increased risk of narrow-angle glaucoma. 4
• Older adults are at particularly high risk for falls, fractures, subdural hematomas, and cognitive impairment from first-generation antihistamines. 4

Appropriate Clinical Context for Hydroxyzine

Hydroxyzine may be considered in specific situations:

• Comorbid pruritus and sleep disturbance. Hydroxyzine 10-25 mg at bedtime can be useful when added to a non-sedating antihistamine regimen for patients with urticaria or dermatologic conditions causing nighttime itching. 5
• Short-term anxiety with insomnia. Hydroxyzine 50 mg has demonstrated efficacy in generalized anxiety disorder with early improvement in cognitive anxiety symptoms. 6 However, benzodiazepine receptor agonists or ramelteon are preferred first-line agents. 3

Recommended Alternative Approach

For a healthy adult with insomnia, the evidence-based treatment algorithm is:

1. First-line: Cognitive Behavioral Therapy for Insomnia (CBT-I) before any medication. 3
2. If pharmacotherapy is necessary: Short/intermediate-acting benzodiazepine receptor agonists (zolpidem 10 mg, eszopiclone 2-3 mg, zaleplon 10 mg) or ramelteon 8 mg are recommended first-line agents. 3
3. Second-line options: Low-dose doxepin 3-6 mg for sleep maintenance or suvorexant for sleep maintenance insomnia. 3

Dosing Adjustments if Hydroxyzine is Used

If hydroxyzine is prescribed despite the above considerations:

• Standard dose: 50 mg at bedtime. 1, 2
• Renal impairment: Halve the dose in moderate renal impairment; avoid in severe renal impairment (CrCl <10 mL/min). 5
• Hepatic impairment: Avoid in severe liver disease due to enhanced sedating effects. 5
• Pregnancy: Contraindicated in early pregnancy; chlorphenamine is preferred if antihistamine therapy is necessary. 5

Common Pitfalls to Avoid

• Do not use hydroxyzine as first-line treatment for chronic insomnia when FDA-approved hypnotics with better safety profiles are available. 3
• Do not assume bedtime dosing eliminates next-day impairment—warn patients about driving and operating machinery. 4
• Do not combine with other CNS depressants (alcohol, benzodiazepines, opioids) as this significantly enhances performance impairment. 4, 5
• Do not use long-term without reassessment—tolerance to sedating effects develops while anticholinergic side effects persist. 4